PMID- 37031518
OWN - NLM
STAT- MEDLINE
DCOM- 20230428
LR  - 20230501
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Linking)
VI  - 174
DP  - 2023 Apr
TI  - Establishment of killer whale (Orcinus orca) primary fibroblast cell cultures and 
      their transcriptomic responses to pollutant exposure.
PG  - 107915
LID - S0160-4120(23)00188-5 [pii]
LID - 10.1016/j.envint.2023.107915 [doi]
AB  - Populations of killer whale (Orcinus orca) contain some of the most polluted 
      animals on Earth. Yet, the knowledge on effects of chemical pollutants is limited 
      in this species. Cell cultures and in vitro exposure experiments are pertinent 
      tools to study effects of pollutants in free-ranging marine mammals. To 
      investigate transcriptional responses to pollutants in killer whale cells, we 
      collected skin biopsies of killer whales from the Northern Norwegian fjords and 
      successfully established primary fibroblast cell cultures from the dermis of 4 
      out of 5 of them. Cells from the individual with the highest cell yield were 
      exposed to three different concentrations of a mixture of persistent organic 
      pollutants (POPs) that reflects the composition of the 10 most abundant POPs 
      found in Norwegian killer whales (p,p'-DDE, trans-nonachlor, PCB52, 99, 101, 118, 
      138, 153, 180, 187). Transcriptional responses of 13 selected target genes were 
      studied using digital droplet PCR, and whole transcriptome responses were 
      investigated utilizing RNA sequencing. Among the target genes analysed, CYP1A1 
      was significantly downregulated in the cells exposed to medium (11.6 microM) and high 
      (116 microM) concentrations of the pollutant mixture, while seven genes involved in 
      endocrine functions showed a non-significant tendency to be upregulated at the 
      highest exposure concentration. Bioinformatic analyses of RNA-seq data indicated 
      that 13 and 43 genes were differentially expressed in the cells exposed to low 
      and high concentrations of the mixture, respectively, in comparison to solvent 
      control. Subsequent pathway and functional analyses of the differentially 
      expressed genes indicated that the enriched pathways were mainly related to lipid 
      metabolism, myogenesis and glucocorticoid receptor regulation. The current study 
      results support previous correlative studies and provide cause-effect 
      relationships, which is highly relevant for chemical and environmental 
      management.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Bjorneset, J
AU  - Bjorneset J
AD  - UiT - The Arctic University of Norway, Tromso, Norway; Norwegian Polar Institute, 
      Fram Centre, Tromso, Norway.
FAU - Blevin, P
AU  - Blevin P
AD  - Akvaplan-niva AS, Fram Centre, Tromso, Norway.
FAU - Bjornstad, P M
AU  - Bjornstad PM
AD  - Oslo University Hospital, Oslo, Norway.
FAU - Dalmo, R A
AU  - Dalmo RA
AD  - UiT - The Arctic University of Norway, Tromso, Norway.
FAU - Goksoyr, A
AU  - Goksoyr A
AD  - Department of Biological Sciences, University of Bergen, Bergen, Norway.
FAU - Harju, M
AU  - Harju M
AD  - Norwegian Institute for Air Research, Fram Centre, Tromso, Norway.
FAU - Limonta, G
AU  - Limonta G
AD  - University of Siena, Siena, Italy.
FAU - Panti, C
AU  - Panti C
AD  - University of Siena, Siena, Italy.
FAU - Rikardsen, A H
AU  - Rikardsen AH
AD  - UiT - The Arctic University of Norway, Tromso, Norway; Norwegian Institute for 
      Nature Research, Tromso, Norway.
FAU - Sundaram, A Y M
AU  - Sundaram AYM
AD  - Oslo University Hospital, Oslo, Norway.
FAU - Yadetie, F
AU  - Yadetie F
AD  - Department of Biological Sciences, University of Bergen, Bergen, Norway.
FAU - Routti, H
AU  - Routti H
AD  - Norwegian Polar Institute, Fram Centre, Tromso, Norway. Electronic address: 
      heli.routti@npolar.no.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230402
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (Environmental Pollutants)
RN  - 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene)
SB  - IM
MH  - Animals
MH  - *Whale, Killer/metabolism
MH  - Environmental Monitoring/methods
MH  - *Environmental Pollutants/toxicity/metabolism
MH  - Transcriptome
MH  - Dichlorodiphenyl Dichloroethylene
MH  - Fibroblasts
MH  - Cell Culture Techniques
OTO - NOTNLM
OT  - Cell culture
OT  - In vitro
OT  - Marine mammal
OT  - Mixture
OT  - Persistent organic pollutant
OT  - RNA-seq
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/04/10 06:00
MHDA- 2023/04/28 06:41
CRDT- 2023/04/09 18:02
PHST- 2022/12/21 00:00 [received]
PHST- 2023/03/27 00:00 [revised]
PHST- 2023/03/31 00:00 [accepted]
PHST- 2023/04/28 06:41 [medline]
PHST- 2023/04/10 06:00 [pubmed]
PHST- 2023/04/09 18:02 [entrez]
AID - S0160-4120(23)00188-5 [pii]
AID - 10.1016/j.envint.2023.107915 [doi]
PST - ppublish
SO  - Environ Int. 2023 Apr;174:107915. doi: 10.1016/j.envint.2023.107915. Epub 2023 
      Apr 2.